DIOSMIN is a naturally occurring flavonoid, which can be obtained from Citrus fruits, or derived semi-synthetically from hesperidin. It is a grey-light yellow coloured hygroscopic powder.

Brief history:
Diosmin was first isolated in 1925 from Scrophularia nodosa, and first introduced as a therapeutic agent in 1969 Diosmin has been used for more than 30 years as a phlebotonic and vascular-protecting agent, and has recently begun to be investigated for other therapeutic purposes, including cancer, premenstrual syndrome, colitis, and diabetes.

Pharmacokinetic effects:
Diosmin is considered to be a vascular-protecting agent used to treat chronic venous insufficiency, hemorrhoids, lymphedema, and varicose veins.As a flavonoid, diosmin also exhibits anti-inflammatory, free-radical scavenging, and antimutagenic properties. Investigations have shown diosmin is rapidly transformed by intestinal flora to its aglycone form, diosmetin. Diosmetin is absorbed and rapidly distributed throughout the body with a plasma half-life of 26-43 hours. Diosmetin is degraded to phenolic acids or their glycine-conjugated derivatives and eliminated through the urine. Diosmin or diosmetin not absorbed is eliminated in the faeces.

Inflammation, Microcirculation & Capillary Permeability:
Diosmin's mechanisms of action include improvement of venous tone, increased lymphatic drainage, protection of capillary bed microcirculation, inhibition of inflammatory reactions, and reduced capillary permeability. Diosmin also seems to be a potent inhibitor of prostaglandin E2 (PGE2) and thromboxane A2 (TxA2) as well as being inhibitor of leukocyte activation, migration, and adhesion. Diosmin causes a significant decrease in plasma levels of endothelial adhesion molecules and reduces neutrophil activation, thus providing protection against microcirculatory damage.

Hemorrhoids / Varicose Veins / Chronic Venous Insufficiency:
Chronic venous insufficiency is characterized by pain, leg heaviness, a sensation of swelling, and cramps, and is correlated with varicose veins. Diosmin-containing flavonoid mixtures have also been effective in treating severe stages of chronic venous insufficiency, including venous ulceration and delayed healing.

Several large clinical trials have demonstrated diosmin to be effective in the treatment of acute and chronic symptoms of hemorrhoids.

Lymphedema:
Diosmin acts on the lymphatic system by increasing lymph flow and lymph oncotic pressure. Animal studies of high-protein lymphedema, such as in burns and lung contusions, showed significant improvement with diosmin.

Diabetes:
Diosmin has been shown to improve factors associated with diabetic complications. Decrease in haemoglobin A1c, accompanied by an increase in glutathione peroxidase (thus demonstrating long-term decreased blood glucose levels and increased antioxidant activity), have also been observed after administration of a diosmin composition. Diosmin can normalize capillary filtration rate and prevent ischemia in diabetics. Rheological studies of type 1 diabetics show diosmin can facilitate hemorheological improvements due to decreased RBC aggregation, which decreases blood flow resistance, resulting in reduction of both stasis and ischemia.

Dermatological, Menstrual & Wound Healing:
Studies have also investigated the use of diosmin for stasis dermatitis, wound healing, premenstrual syndrome, mastodynia, dermatofibrosclerosis, viral infections, and colitis. More clinically oriented research is indicated.

Drug-Nutrient Interactions:
Diosmin can cause a decrease in RBC aggregation and blood viscosity. There are no documented cases of adverse interactions between diosmin and prescription medications, but caution should be taken when combining diosmin with aspirin or other blood-thinning medications. Data suggest that diosmin has an inhibitory effect on cytochrome P450-mediated metabolism in healthy volunteers which may alter the pharmacokinetics of drugs taken concomitantly. Patients given metronidazole after nine days of pre-treatment with 450 m diosmin demonstrated changes in serum concentrations of metronidazole, as well as changes in urinary concentrations of metronidazole and its metabolism.

Side Effects and Toxicity:
In animal studies, a flavonoid mixture containing 90-percent diosmin and 10-percent hesperidin had an L[D.sub.50] of more than 3g/kg. In addition, animal studies have shown the absence of acute, subacute, or chronic toxicity after repeated oral dosing for 13 and 26 weeks using a dose representing 35 times the recommended daily dose.

Diosmin is considered to have no mutagenic activity, embryo toxicity, nor any significant effect on reproductive function. Transplacental migration and passage into breast milk are mini-real. Researchers believe that hesperidin and diosmin interfere with arachidonic acid metabolism and histamine release. The flavonoids also inhibit thromboxane and prostaglandin activation. These actions prevent inflammatory responses from occurring, and some believe that the substance may minimize allergic reactions.